Background: High-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are established biomarkers in cardiology. While hs-cTn is crucial for diagnosing myocardial necrosis, and NT-proBNP reflects hemodynamic stress, their combined utility for risk stratification in a broad acute coronary syndrome (ACS) population is not fully defined. Methods: We conducted a prospective, single-center cohort study enrolling consecutive patients admitted with a diagnosis of ACS (ST-elevation myocardial infarction [STEMI] or non-ST-elevation ACS [NSTE-ACS]). Admission blood samples were analyzed for hs-cTnT and NT-proBNP. Patients were categorized into four groups based on established cut-off values: Group 1 (normal hs-cTnT/normal NT-proBNP), Group 2 (elevated hs-cTnT/normal NT-proBNP), Group 3 (normal hs-cTnT/elevated NT-proBNP), and Group 4 (elevated hs-cTnT/elevated NT-proBNP). The primary endpoint was a composite of MACE, including all-cause mortality, non-fatal myocardial infarction, and urgent revascularization within 6 months. Results: A total of 482 patients were included in the final analysis (mean age 64.2 ± 11.8 years; 68.9% male). The incidence of MACE at 6 months was significantly different across the four groups. MACE occurred in 3.5% of patients in Group 1 (n=114), 12.8% in Group 2 (n=172), 15.2% in Group 3 (n=66), and 34.6% in Group 4 (n=130) (p < 0.001 for overall comparison). Patients with dual biomarker elevation (Group 4) had a significantly higher risk of MACE compared to all other groups. In a multivariate Cox proportional hazards model adjusted for traditional risk factors, dual elevation of hs-cTnT and NT-proBNP remained the strongest independent predictor of MACE (Hazard Ratio: 4.12, 95% Confidence Interval: 2.55–6.65, p < 0.001). Conclusion: The combined assessment of hs-cTn and NT-proBNP on admission provides powerful synergistic prognostic information in patients with ACS. This dual biomarker strategy effectively identifies a very high-risk subgroup of patients who may benefit from more intensive monitoring and therapeutic interventions.